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1.
J Int Med Res ; 48(10): 300060520964009, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100064

RESUMO

BACKGROUND: The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation.Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery. CONCLUSION: Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.


Assuntos
Lesão Renal Aguda/patologia , Infecções por Coronavirus/patologia , Transplante de Rim/efeitos adversos , Rim/patologia , Pneumonia Viral/patologia , Lesão Renal Aguda/virologia , Adulto , Betacoronavirus , Esquema de Medicação , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Transplantados , gama-Globulinas/administração & dosagem , gama-Globulinas/uso terapêutico
2.
Medicine (Baltimore) ; 99(44): e22931, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126356

RESUMO

RATIONALE: Synchronous development of both anaplastic large cell lymphoma (ALCL) and multiple myeloma (MM) in a patient is rare. To our knowledge, until now only one case has been reported. Treatment needs to cover both and is a challenge. Here we reported another case and discussed the diagnosis and treatment. PATIENT CONCERNS: This is a 63-year old woman who presented with a mass in upper abdominal skin. Positron emission tomography/computed tomography (PET/CT) showed the high metabolism in left abdominal skin and left axillary lymph nodes. Histopathologic and immunohistochemical evaluation identified the cutaneous mass as an ALK-negative ALCL. Bone marrow smear showed increased plasma cells which expressed CD38, CD138, and cLambda concomitantly. The increased monoclonal immunoglobulin IgD λ was detected by immunofixation electrophoresis. DIAGNOSES: Diagnosis of both ALCL and MM was confirmed. INTERVENTIONS: The patient successively received 6 cycles of B-CHOD regimen, one cycle of ID regimen, 2 cycles of DHAX regimen, one cycle of L-DA-EPOCH and autologous stem cell transplantation (ASCT). Then lenalidomide was performed as a maintenance therapy. OUTCOMES: Both ALCL and MM achieved complete remission. LESSONS: We reported a very rare case with synchronous development of ALCL and MM, in whom a good therapeutic response to chemotherapies followed by ASCT has been observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Lenalidomida/administração & dosagem , Linfoma Anaplásico de Células Grandes , Mieloma Múltiplo , Neoplasias Cutâneas , Parede Abdominal/patologia , Bleomicina/administração & dosagem , Exame de Medula Óssea/métodos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/imunologia , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/terapia , Quimioterapia de Manutenção/métodos , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Indução de Remissão , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Transplante Autólogo/métodos , Vincristina/administração & dosagem
4.
Ann Hematol ; 99(10): 2429-2436, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839869

RESUMO

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Agonistas dos Canais de Cloreto/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Lubiprostona/uso terapêutico , Linfoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alcaloides de Vinca/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Constipação Intestinal/induzido quimicamente , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Famotidina/uso terapêutico , Feminino , Humanos , Laxantes/farmacologia , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Entorpecentes/efeitos adversos , Prednisona/administração & dosagem , Pontuação de Propensão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Senosídeos/uso terapêutico , Alcaloides de Vinca/administração & dosagem , Vincristina/administração & dosagem
5.
J Gastrointestin Liver Dis ; 29(3): 470, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32830825
6.
Am J Case Rep ; 21: e926475, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32692733

RESUMO

BACKGROUND Autoimmune pancreatitis (AIP) is a rare, steroid-responsive disease of the pancreas. Concurrent treatment with immunosuppressants, including corticosteroids, increases the risk of developing a severe form of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) advises against the use of corticosteroids in patients with SARS-CoV-2 due to their poor outcomes in patients with SARS-CoV and Middle East respiratory syndrome (MERS-CoV), unless these patients require steroid treatment for a coexisting disease. CASE REPORT A 53-year old patient was admitted with symptoms and diagnostic findings consistent with AIP. Thorough etiological workup revealed an elevated IgG4 level of 361 mg/dL and significant clinical response to corticosteroid treatment, leading to a diagnosis of AIP. After finishing steroid treatment at home, the patient was readmitted with another episode of AIP complicated by development of acute necrotic collection and COVID-19 while taking a second course of high dose prednisone. The patient was continued on high dose prednisone, started on azathioprine and intravenous meropenem, and underwent CT guided percutaneous drainage. He also received supportive care for COVID-19. After significant clinical improvement, the patient was discharged to quarantine at home, which he completed uneventfully. CONCLUSIONS Despite the use of corticosteroids due to AIP, this high risk patient recovered from COVID-19 without complications. These findings support the use of corticosteroids when necessary for treatment of coexisting conditions in COVID-19 patients.


Assuntos
Pancreatite Autoimune/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Prednisona/administração & dosagem , Pancreatite Autoimune/tratamento farmacológico , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
7.
BMJ Case Rep ; 13(7)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641443

RESUMO

This is a case of a patient who presented with an urticarial rash 48 hours before developing symptoms of fever and a continuous cough. She subsequently developed angioedema of her lips and hands before testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Urticarial rashes occurring 48 hours before other symptoms of COVID-19 infection have been documented. This case demonstrates the importance of heightened awareness that not all urticarial rashes represent spontaneous urticaria and as a consequence, this may result in misdiagnosis and ultimately delayed diagnosis. This is the first reported case in the literature of urticaria with angioedema as a prodromal phenomenon of COVID-19.


Assuntos
Angioedema , Clorfeniramina/administração & dosagem , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Prednisona/administração & dosagem , Terfenadina/análogos & derivados , Urticária , Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/fisiopatologia , Antialérgicos/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Sintomas Prodrômicos , Terfenadina/administração & dosagem , Resultado do Tratamento , Urticária/diagnóstico , Urticária/etiologia , Urticária/fisiopatologia
8.
Lancet ; 396(10246): 267-276, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711802

RESUMO

BACKGROUND: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. METHODS: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. FINDINGS: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. INTERPRETATION: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. FUNDING: F Hoffmann-La Roche.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão/métodos , Administração Intravenosa , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/etnologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , França/epidemiologia , Alemanha/epidemiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Subcutâneas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Federação Russa/epidemiologia , Sérvia/epidemiologia , Tunísia/epidemiologia
9.
Ann Hematol ; 99(8): 1771-1778, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32601796

RESUMO

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma de Célula do Manto/terapia , Sirolimo/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidade , Vincristina/administração & dosagem , Vincristina/efeitos adversos
10.
Trials ; 21(1): 632, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646502

RESUMO

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. INCLUSION CRITERIA: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients' medical records. EXCLUSION CRITERIA: - Oxygen desaturation below 93% or P02 < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title "OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE" with EudraCT number 2020-001622-64 , registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Corticosteroides/administração & dosagem , Assistência Ambulatorial , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Prednisona/administração & dosagem , Adolescente , Corticosteroides/efeitos adversos , Adulto , Idoso , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prednisona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Ann Hematol ; 99(10): 2377-2384, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32728938

RESUMO

This study investigated the prognostic value of 25-hydroxy vitamin D (25-(OH)D) deficiency and the association between 25-(OH)D deficiency and c-Myc positivity in 208 newly diagnosed diffuse large B cell lymphoma (DLBCL) patients. 25-(OH)D deficiency was defined as serum 25-(OH)D level lower than 52.5 nmol/L. Using cutoff values of 40%, positive tumor cells for c-Myc expression was established. One hundred forty-two patients had 25-(OH)D deficiency and 70 had c-Myc positivity with a median follow-up of 29 months (range, 16 to 49 months) in this cohort. Multivariate Cox regression analysis showed that 25-(OH)D deficiency was an independent prognostic predictor for inferior progression-free survival (PFS) (P = 0.001) and overall survival (OS) (P = 0.006), and c-Myc positivity was an unfavorable prognostic factor for PFS (P = 0.004). In addition, c-Myc positivity was more frequent in patients with 25-(OH)D deficiency (P = 0.027). Moreover, we found that the presence of c-Myc positivity could aggravate the adverse effects of 25-(OH)D deficiency for PFS time (P = 0.0045). 25-(OH)D deficiency together with IPI (IPI-D) improved the prognostic capacity compared with only IPI in predicting the risk of DLBCL which was assessed by the calculation of receiver operator characteristic (ROC) curves and the areas under the curve (AUC). Noteworthy, c-Myc positivity combined with IPI-D was better than IPI-D in predicting PFS time. In summary, 25-(OH)D deficiency was a strong prognostic factor in DLBCL. Further multi-center prospective studies are needed to confirm the results and better understand the underlying mechanisms.


Assuntos
Genes myc , Linfoma Difuso de Grandes Células B/epidemiologia , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , China/epidemiologia , Comorbidade , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prednisona/administração & dosagem , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-myc/genética , Curva ROC , Vincristina/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto Jovem
12.
Neurology ; 95(6): e755-e766, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32611638

RESUMO

OBJECTIVE: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG). METHODS: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups. RESULTS: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. CONCLUSIONS: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. CLINICALTRIALSGOV IDENTIFIER: NCT00294658. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.


Assuntos
Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Prednisona/uso terapêutico , Timectomia , Adolescente , Adulto , Animais , Terapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/cirurgia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Ratos , Método Simples-Cego , Síndrome de Abstinência a Substâncias/etiologia , Timoma/complicações , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Adulto Jovem
13.
Int J Hematol ; 112(3): 385-394, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32519171

RESUMO

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma often with extranodal involvement at diagnosis, and yet how this feature correlates with survival awaits elucidation. To address this issue, a correlative analysis between clinical features of 127 MCL patients and their overall survival (OS) was conducted. In this cohort, the median age at MCL diagnosis was 62 years and 81% were males. Eighty-four percent of patients were Ann Arbor stage 4, and 15% were blastoid variants. In patients with gastrointestinal MCL, approximately 40% had gastric involvement. In treatment, CHOP-based induction chemotherapy was given to 61.1% of patients. One-third of patients undertook autologous stem cell transplant (SCT), and 4.7% had allogeneic SCT. The median OS was 82 months and well-stratified in MIPI risk groups. In the multivariate analysis for OS, blastoid variants and gastric involvement were both independent risk factors whereas auto-SCT had a protective effect. Overall, this study corroborated with the current understandings and international therapeutic standards for MCL. Auto-SCT associated with a better OS while allo-SCT remained an option for blastoid variants and those who failed Auto-SCT. Interestingly, patients with gastric involvement tended to have worse survival, a finding that spawns more studies to investigate the mechanism.


Assuntos
Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/terapia , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Indução de Remissão , Transplante de Células-Tronco , Taiwan/epidemiologia , Transplante Autólogo , Transplante Homólogo , Vincristina/administração & dosagem
14.
Medicine (Baltimore) ; 99(25): e20832, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569233

RESUMO

BACKGROUND: The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically. METHODS: According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives. RESULTS: This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma. CONCLUSION: The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG. PROSPERO REGISTRATION NUMBER: CRD 42020167735.


Assuntos
Anti-Inflamatórios/uso terapêutico , Miastenia Gravis/terapia , Prednisona/uso terapêutico , Timectomia , Anti-Inflamatórios/administração & dosagem , Terapia Combinada , Humanos , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/cirurgia , Prednisona/administração & dosagem , Timectomia/efeitos adversos , Timectomia/métodos , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(22): e20367, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481418

RESUMO

BACKGROUND: Previous studies have reported that docetaxel combined prednisone (DP) has been used for the treatment of patients with hormone refractory prostate cancer (HRPC). However, its results are still inconsistent. Therefore, this study will synthesize the latest evidence of the efficacy and safety of DP for the treatment of patients with HRPC. METHODS: Cochrane Library, PUBMED, EMBASE, Web of Science, CINAHL, CBM, and CNKI will be searched to identify randomized controlled trials published from their inception to the March 1, 2020, irrespective language and publication time restrictions. We will calculate the pooled effects of dichotomous outcomes as risk ratio and 95% confidence intervals, and that of continuous outcomes as standardized mean difference or mean difference and 95% confidence intervals. Study quality will be assessed using Cochrane risk of bias, and quality of evidence for main outcome will be evaluated using Grading of Recommendations Assessment Development and Evaluation. Statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will appraise the efficacy and safety of DP for the treatment of patients with HRPC. The primary outcome includes overall survival, and the secondary outcomes comprise of progression-free survival, prostate-specific antigen response rate, duration of prostate-specific antigen response, objective tumor response rate, disease-free survival, quality of life, and adverse events. CONCLUSION: The results of this study may provide helpful evidence of DP for the treatment of patients with HRPC.Systematic review registration: INPLASY202040112.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Docetaxel/uso terapêutico , Prednisona/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Humanos , Masculino , Prednisona/administração & dosagem
19.
Ann Hematol ; 99(8): 1823-1831, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32577843

RESUMO

Although overall survival in diffuse large B cell lymphomas (DLBCL) has improved, central nervous system (CNS) relapse is still a fatal complication of DLBCL. For this reason, CNS prophylaxis is recommended for patients at high risk of CNS disease. However, no consensus exists on definition of high-risk patient and optimal CNS prophylaxis. Systemic high-dose methotrexate in combination with R-CHOP has been suggested as a potential prophylactic method, since methotrexate penetrates the blood-brain barrier and achieves high concentration in the CNS. In this retrospective analysis, we report treatment outcome of 95 high-risk DLBCL/FL grade 3B patients treated with R-CHOP or its derivatives with (N = 57) or without (N = 38) CNS prophylaxis. At a median follow-up time (51 months), CNS relapses were detected in twelve patients (12.6%). Ten out of twelve (83%) of CNS events were confined to CNS system only. Median overall survival after CNS relapse was 9 months. Five-year isolated CNS relapse rates were 5% in the prophylaxis group and 26% in the group without prophylaxis. These findings suggest that high-dose methotrexate-containing prophylaxis decreases the risk of CNS failure.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/prevenção & controle , Metotrexato/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Rituximab/administração & dosagem , Vincristina/administração & dosagem
20.
J Cancer Res Clin Oncol ; 146(11): 2995-3002, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32524293

RESUMO

BACKGROUND: Comorbidity and relative dose intensity (RDI) have been associated with survival in diffuse large B-cell lymphoma (DLBCL) patients, but both relationships remain unaddressed in the same patients. METHODS: A retrospective review of consecutive DLBCL patients treated from January 2010 to October 2018 was performed. Data for the clinical characteristics of the patients, including the Charlson Comorbidity Index (CCI) and RDI, on their outcomes were evaluated. RESULTS: A total of 211 patients with a median age of 72 years (range 19-90 years) were analyzed. CCI ≥ 2 was associated with poor event-free survival (EFS) and overall survival (OS). RDI < 70% was associated with worse EFS and OS. A multivariate analysis revealed that RDI < 70% was only a poor risk factor for the reduction of OS in elderly DLBCL patients (65 years <) and independent from the presence of CCI. The relationship between CCI and RDI in elderly patients was analyzed in four groups, based on CCI ≥ 2 or less and RDI ≥ 70% or less. The group with CCI ≥ 2 and RDI < 70% had a poorer OS and EFS, as compared to the other three groups. The group with CCI < 2 and RDI ≥ 70% had a superior OS but an identical EFS, as compared to the two groups with CCI < 2 and RDI < 70% and CCI ≥ 2 and RDI ≥ 70%. CONCLUSIONS: CCI ≥ 2 was associated with a poorer outcome, but maintaining RDI ≥ 70% may improve the outcome, especially in elderly DLBCL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Rituximab/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
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